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1.
Michael B. Rothberg Bo Hu Laura Lipold Sarah Schramm Xian Wen Jin Andrea Sikon Glen B. Taksler 《Cancer causes & control : CCC》2018,29(3):297-304
Importance
Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.Objective
To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.Design
The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.Setting
The study was conducted in a setting of 33 primary care practices from 2004 to 2010.Participants
The participants of the study were women aged ≥?30 years.Main outcome and measures
CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.Results
The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).Conclusions and relevance
A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.2.
Anat Gafter-Gvili Michal Herman Yaacov Ori Asher Korzets Avry Chagnac Boris Zingerman Benaya Rozen-Zvi Uzi Gafter Tsipora Malachi 《Leukemia research》2011,35(2):219-225
Background
Mitochondria provide ATP and Ca2+ needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA.Aim
To investigate the effect of mitochondrial function inhibition on DNA repair.Method
Five mitochondrial inhibitors acting at various sites of electron transport were studied. Human peripheral blood mononuclear cells, spontaneous and H2O2-indcued DNA repair, as well as %-double-stranded-DNA, were measured.Results
All mitochondrial inhibitors suppressed spontaneous and H2O2-induced DNA repair. However, their effect on %-double-stranded-DNA differed, which is partly related to ROS suppression.Conclusion
Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy. 相似文献3.
Cletus A. Arciero Jing Yang Limin Peng Kevin C. Ward Ruth O’Regan Aysegul A. Sahin Xiaoxian Li 《Breast cancer research and treatment》2017,166(3):743-755
Purpose
Racial disparity of breast cancer in each subtype and substage is not clear.Methods
We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2?, HR+/HER2+, HR?/HER2+, and HR?/HER2?.Results
African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2? stages III and IV breast cancer and HR?/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2? stage II cancer and HR?/HER2? stage II cancer.Conclusion
AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.4.
M.- J. Zhang C.- Z. Zhang W.- J. Du X.- Z. Yang Z.- P. Chen 《Clinical & translational oncology》2016,18(8):776-781
Objective
ATPase family, AAA domain containing 2 (ATAD2) has been found overexpressed in various cancer types and correlated with malignant status and poor prognosis. However, little is known about the clinical significance of ATAD2 in gastric cancer patients. The aim of this study was to explore the clinical and prognostic significance of ATAD2 in gastric cancer.Methods
The mRNA and protein levels expression of ATAD2 were detected in clinical tissue samples by qRT-PCR and immunohistochemistry, respectively. We examined the ATAD2 protein expression by immunohistochemistry. Furthermore, we analyzed the association between ATAD2 expression and clinicopathological features including prognosis in 166 gastric cancer samples.Results
In our results, ATAD2 mRNA and protein were highly expressed in gastric cancer samples. ATAD2 overexpression was correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis. According to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastric cancer patients.Conclusions
In summary, ATAD2 could serve as a prognostic biomarker for gastric cancer patients.5.
Jordan Lerner-Ellis Humayun Ahmed Sophia George Gilian Wharfe Sheray Chin Dwight Lowe Robert Royer Shiyu Zhang Steven Narod Judith Hurley Mohammad R. Akbari 《Breast cancer research and treatment》2017,162(3):591-596
Purpose
Jamaica is an island nation with one of the highest breast cancer incidence rates in the Caribbean (40/100,000 per year). The contribution of cancer susceptibility gene mutations to the burden of breast cancer in Jamaica has not yet been explored. We sought to determine the prevalence of germline mutations in BRCA1, BRCA2, and PALB2 in 179 unselected Jamaican women with breast cancer.Methods
We sequenced the entire coding regions of BRCA1, BRCA2, and PALB2 for all the study subjects.Results
Overall, 8 of 179 patients (4.5%) had a mutation in one of the three genes: one in BRCA1, two in BRCA2, and five in PALB2.Conclusions
These data suggest that in addition to BRCA1 and BRCA2, PALB2 should be included in genetic testing for breast cancer patients in Jamaica.6.
Background:
The aim of this study is to evaluate distribution and clinical impact of the SS18-SSX fusion gene in patients with synovial sarcoma in China.Methods:
We collected and analysed the clinical data of 88 patients using univariate and multivariate survival analysis. HEK 293T and NIH 3T3 cell lines were transfected with the SS18-SSX1 or SS18-SSX2 gene to determine the respective involvement of these fusion genes in cell proliferation and invasion.Results:
Overall survival was significantly better among SS18-SSX2 cases (P=0.001), FNCLCC grade 2 cases (P<0.001), and UICC stage 1 or 2 (P<0.001) by univariate and multivariate survival analysis. SS18-SSX1-positive cells were more proliferative and invasive than SS18-SSX2-positive cells.Conclusion:
SS18-SSX fusion type is a significant prognostic factor for patients with synovial sarcoma. 相似文献7.
GholamReza Karami Madani Abolfazl Rad Mehdi Molavi Sima Ardalan Khales Mohammad Reza Abbaszadegan Mohammad Mahdi Forghanifard 《Journal of gastrointestinal cancer》2018,49(4):437-441
Background
Enhancer of zeste homolog 2 (EZH2), a stemness factor, plays roles in regulation of cell differentiation and embryonic development as well as cancer progression. Deregulation of EZH2 in cancers is correlated with tumor cell invasiveness, metastasis, and the patients’ poor outcome. However, the mechanistic role of EZH2 in cancer is ambiguous. In this study, we aimed to inhibit the expression of EZH2 in a cancer cell line, and evaluate consequence changes in gene expression pattern.Materials and methods
Using specific retroviral shRNA-EZH2, EZH2 gene was silenced in the KYSE30 cell line. Relative comparative real-time PCR was used to confirm silencing of EZH2 and evaluate expression pattern of selected markers.Results
Inhibition of EZH2 expression in KYSE30 cells caused significant changes in different genes. Indeed, HIWI and HEY1 genes were over- and underexpressed in KYSE30 cells, respectively, following EZH2 silencing. Other selected cancer stem cell markers were not changed significantly.Conclusion
To the best our knowledge, there are variety of small molecule inhibitors to target EZH2 in cancer cells as a treatment candidate; therefore, our data in this study helps the researchers to select EZH2 for cancer therapy based on its mechanism and correlation with other markers.8.
Background
Ubiquitin-associated protein 2-like (UBAP2L) contains a ubiquitin-associated domain near its N-terminus, which has been demonstrated to be overexpressed in multiple tumors, including hepatocellular carcinoma and colorectal carcinoma but its role has not been well studied in breast cancer. Thus, this study was designed to evaluate whether UBAP2L can serve as a potential molecular target for breast cancer therapy.Methods
The expression of UBAP2L was determined in breast cancer tissues and cell lines by Western blotting and Oncomine database mining. Then the expression of UBAP2L was silenced using RNA interference and the effects of UBAP2L knockdown on breast cancer cell proliferation and cell cycle progression by MTT and colony formation assay, and Flow cytometry, respectively.Results
We found the expression of UBAP2L was significantly up-regulated in breast cancer tissues and cell lines. Knockdown of UBAP2L suppressed cell proliferation, impaired colony formation ability and induced cell cycle arrest at G2/M phase. At molecular levels, knockdown of UBAP2L increased p21 expression, but decreased the expression of CDK1 and Cyclin B1 in breast cancer cells.Conclusion
Our findings suggest that UBAP2L plays an important role in breast cancer cell proliferation and might serve as a potential target for breast cancer treatment.9.
Hiroshi Nakagomi Ikuko Sakamoto Yosuke Hirotsu Kenji Amemiya Hitoshi Mochiduki Masao Omata 《International journal of clinical oncology / Japan Society of Clinical Oncology》2016,21(2):270-275
Background
PALB2 (Partner and Localizer of BRCA2) was identified as a moderate-risk gene in breast and pancreatic cancers. Recently, it was reported that PALB2 carriers have a high risk of developing breast cancer, with the cumulative risk of 34 % by the age of 70.Patients and methods
Peripheral blood samples from 155 patients at risk for hereditary breast and/or ovarian cancer were tested for BRCA1/2 and PALB2 by targeted sequencing using a next-generation sequencer. Of these 155, 146 met NCCN criteria and the remaining 9 did not.Results
BRCA1/2 analysis was performed on 155 patients, for whom the results were reported previously (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). Eleven patients were identified to have deleterious BRCA mutations (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). However, none of the 155 patients were found to have deleterious PALB2 germline mutations. Missense mutations [variants of uncertain significance (VUS)] of PALB2 were found in 12 cases. In silico analyses by SIFT (Sorting Intolerant Form Tolerant) and PolyPhen2 (Polymorphism Phenotyping version 2) indicated that 2 of 12 VUS were deleterious and probably damaging.Conclusions
This is the first report on PALB2 mutations in Japan, revealing two missense mutations as “deleterious and probably damaging” by in silico analyses, but no PALB2 premature truncation mutations were identified. The sample size is relatively small and a larger cohort study is needed in Japan.10.
M Miyamoto M Takano K Iwaya N Shinomiya T Goto M Kato A Suzuki T Aoyama J Hirata I Nagaoka H Tsuda K Furuya 《British journal of cancer》2015,112(4):739-744
Background:
High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers.Methods:
Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters.Results:
Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P<0.01). In addition, negative HtrA2 expression was identified as an independent worse prognostic factor for progression-free survival and overall survival by multivariate analyses. Furthermore, HtrA2 downregulation modulated sensitivity to platinum in serous ovarian cancer cells in vitro.Conclusions:
HtrA2 expression was a predictor for sensitivity to chemotherapy, and could be a candidate of molecular target in the treatment of high-grade serous ovarian cancers. 相似文献11.
M Iwatsuki K Toyoshima M Watanabe N Hayashi T Ishimoto K Eto S Iwagami Y Baba N Yoshida A Hayashi Y Ohta H Baba 《British journal of cancer》2013,109(11):2829-2832
Background:
The clinical significance of circulating tumour cell (CTC) detection in gastrointestinal (GI) cancer remains controversial and the molecular biological characteristics of CTCs are poorly understood.Methods:
A total of 87 patients with metastatic or recurrent GI cancer were prospectively enrolled. Circulating tumour cells and their HER2 status were assessed using the CellSearch System.Results:
Among the 62 CTC-positive cases, we found 22 discordant cases (35.5%). Among the HER2-negative primary tumours, 17 of 54 developed HER2-positive CTCs. Five of eight had HER2-negative CTCs among the HER2-positive primary tumours.Conclusion:
The findings in the current study suggest that it is critical to evaluate the HER2 status of not only the primary tumour but also the CTCs because the metastasising tumour cells are the primary target of systemic therapy. 相似文献12.
13.
C. Zhang C. Li X. Chen Y. Zhou B. Yin R. Ni Y. Zhang J. Liu 《Clinical & translational oncology》2017,19(12):1507-1517
Purpose
Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear.Methods
Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion.Results
Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling.Conclusions
Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.14.
AnLi Zhang Hua Xue XiaoGuang Ling Yi Gao Feng Yang LianSheng Cheng Jing Liu Qiang Wu 《Journal of experimental & clinical cancer research : CR》2010,29(1):23
Background and Aims
Anti-HER-2 antibodies targeting distinct epitopes have different biological functions on cancer cells. In a previous study, we demonstrated that anti-HER-2 engineering antibody ChA21 was able to bind to subdomain I of HER-2 extracellular domain. In this study, The effects of ChA21 on growth and apoptosis against ovarian carcinoma cell SK-OV-3 over-expressing HER-2 in vitro and in vivo were investigated.Methods
Cell growth inhibition was evaluated by MTT assay. Apoptosis was detected by TUNEL stain, transmission electron microscopy and flow cytometry on cultured cells and tissue sections from nude mice xenografts. The apoptosis-related proteins Bax and Bcl-2 were assessed by immunohistochemistry.Results
We found that treatment of ChA21 caused a dose-dependent decrease of cell proliferation in vitro and a significant inhibition of tumor growth in vivo. ChA21 therapy led to a significant increase in the induction of apoptosis, and up-regulated the expression of Bax, while the expression of Bcl-2 was down-regulated.Conclusion
These data suggest that ChA21 inhibits the growth and induces apoptosis of SK-OV-3 via regulating the balance between Bax and Bcl-2. 相似文献15.
Florence Huguet Nicole Giocanti Vincent Favaudon Annette K. Larsen 《Targeted oncology》2016,11(3):371-381
Background
Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients.Objective
Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells.Methods
The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis.Results
Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS wt) and Capan-2 (KRAS mut) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio-induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS mut) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization.Limitations
These results must be confirmed in vivo.Conclusions
Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status.16.
Shu Li XiaoXin Ma Li Ma Cuicui Wang YuanQi He ZhiJuan Yu 《Journal of experimental & clinical cancer research : CR》2013,32(1):11
Objectives
To investigate the role of HER-2/neu-mediated COX-2/P450arom signal in estrogen-dependent endometrial carcinoma.Methods
The recombinant eukaryotic expression vector, pcDNA3.1-HER-2/neu, was constructed and transfect to Ishikawa endometrial carcinoma cells. The expression of COX-2 and P450arom in transfected cells were detected by real-time PCR and western blotting. The levels of estrogen in cell supernatants were detected by ELISA.Results
Over-expression of HER-2/neu in transfected cells was confirmed by real-time PCR and western blotting. The levels of autocrine estrogen in transfected cells was significantly increased which combination with the enhancement of COX-2 and P450arom expression in transfected cells.Conclusion
HER-2/neu induced the improvement of autocrine estrogen in endometrial carcinoma cell through triggering the COX-2/P450arom signal. 相似文献17.
M Quintela-Fandino A Urruticoechea J Guerra M Gil A Gonzalez-Martin R Marquez E Hernandez-Agudo C Rodriguez-Martin M Gil-Martin R Bratos M J Escudero S Vlassak F Hilberg R Colomer 《British journal of cancer》2014,111(6):1060-1064
Introduction:
Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer.Methods:
Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method).Results:
The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%.Conclusions:
The combination allows the delivery of full-dose intensity, while efficacy seems promising. 相似文献18.
19.
Background
Some tumour suppressor genes (BRCA2) and mismatch repair genes (MSH2, MLH1) are correlated with an increased risk for male breast cancer.Case report
Our patient developed secondary breast cancer after the treatment for Hodgkin’s disease in childhood. DNA was isolated from the patients’ blood and screened for mutations, polymorphisms and variants in BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes. We found no mutations but common polymorphisms, and three variants in mismatch repair genes.Conclusions
Nucleotide variants c.2006-6T>C and p.G322D in MSH2 might be correlated with male breast cancer. 相似文献20.
J Kurashige M Watanabe M Iwatsuki K Kinoshita S Saito Y Nagai T Ishimoto Y Baba K Mimori H Baba 《British journal of cancer》2012,107(8):1233-1238